Abstract
In order to evaluate the usefulness of cocktails of labeled monoclonal antibodies (MoAbs) recognizing different antigen molecules to localize human cancer xenografts, we have compared the potential of three MoAbs recognizing representative cancer‐associated CA 19–9, 17–1A and CEA antigens when administered alone or in combination. Specific binding of radioiodinated F(ab′)2 fragments of these three MoAbs was observed to human colorectal cancer cell lines SW1116, LS180 and Co‐3. The percentage of in vitro cell binding of a cocktail of any two MoAbs to cancer cells was equal to the average of those obtained with the two MoAbs alone. The three MoAbs were preferentially localized in tumor tissues xenografted in nude mice. When cocktails of any two MoAbs were used, the obtained tumor‐to‐normal tissue ratios and percent of injected dose per gram of tumor were between the levels obtained for each MoAb when administered alone, in all three tumors transplanted in nude mice. These data suggest that, although cocktails of labeled MoAbs recognizing different antigens may extend the spectrum of tumor specificities, their use does not improve the tumor localization ability of MoAb‐conjugates.
Keywords: Monoclonal antibody cocktail, CA 19–9, 17‐1A, Carcinoembryonic antigen, Tumor targeting
Full Text
The Full Text of this article is available as a PDF (392.7 KB).
REFERENCES
- 1. ) Abdel‐Nabi , H. H. , Schwartz , A. N. , Higano , C. S. , Wechter , D. G. and Unger , M. W.Colorectal carcinoma: detection with idium‐111 anticarcinoembryonic‐antigen monoclonal antibody ZCE‐025 . Radiology , 164 , 617 – 621 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Murray , J. L. , Rosenblum , M. G. , Sobol , R. E. , Bartholomew , R. M. , Plager , C. E. , Haynie , T. P. , Jahns , M. F. , Glenn , H. J. , Lamki , L. , Benjamin , R. S. , Papadopoulos , N. , Boddie , A. W. , Frincke , J. M. , David , G. S. , Carlo , D. J. and Hersh , E. M.Radioimmunoimaging in malignant melanoma with 111In‐labeled monoclonal antibody 96.5 . Cancer Res. , 45 , 2376 – 2381 ( 1985. ). [PubMed] [Google Scholar]
- 3. ) Baum , R. P. , Maul , F. D. , Senekowitsch , R. , Lorenz , M. , Hottenrott , C. , Happ , J. , Standke , R. , Chatal , J. F. , Saccavini , J. C. , Kriegel , H. and Hor , G.Radio‐immunoscintigraphy of CA19‐9/CEA producing tumors using I‐131 labeled F(ab′)2 fragments of monoclonal antibodies (19‐9/anti‐CEA radioimmunococktail) . In “ Nuclear Medicine in Clinical Oncology ,” ed. Winkler C. , pp. 197 – 206 ( 1986. ). Springer‐Verlag; , Berlin, Heidelberg . [Google Scholar]
- 4. ) Dillman , R. O. , Shawler , D. L. , Johnson , D. E. , Meyer , D. L. , Koziol , J. A. and Frincke , J. M.Preclinical trials with combinations and conjugates of T101 monoclonal antibody and doxorubicin . Cancer Res. , 46 , 4886 – 4891 ( 1986. ). [PubMed] [Google Scholar]
- 5. ) Spitler , L. E. , Del‐Rio , M. , Khentigan , A. , Wedel , N. I. , Brophy , N. A. , Miller , L. L. , Harkonen , W. S. , Rosendorf , L. L. , Lee , H. M. , Mischak , R. P. , Kawahata , R. T. , Stoudemire , J. B. , Fradkin , L. B. , Bautista , E. E. and Scannon , R. J.Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody‐ricin A chain immunotoxin . Cancer Res. , 47 , 1717 – 1723 ( 1987. ). [PubMed] [Google Scholar]
- 6. ) Gaffar , S. A. , Pant , K. D. , Shochat , D. , Bennett , S. J. and Goldenberg , D. M.Experimental studies of tumor radio‐immunodetection using antibody mixtures against carcino‐embryonic antigen (CEA) and colon‐specific antigen‐p (CSAp) . Int. J. Cancer , 27 , 101 – 105 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Ceriani , R. L. and Blank , E. W.Experimental therapy of human breast tumors with 131I‐labeled monoclonal antibodies prepared against the human milk fat globule . Cancer Res. , 48 , 4664 – 4672 ( 1988. ). [PubMed] [Google Scholar]
- 8. ) Chatal , J. F. , Saccavini , J. C. , Fumoleau , P. , Douillard , J. Y. , Curtet , C. , Kremer , M. , Mevel , B. E. and Koprowski , H.Immunoscintigraphy of colon carcinoma . J. Nucl. Med. , 25 , 307 – 314 ( 1984. ). [PubMed] [Google Scholar]
- 9. ) Douillard , J. Y. , Lehur , P. A. , Aillet , G. , Kremer , M. , Bianco‐Arco , A. , Peltier , P. and Chatal , J. F.Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract . Cancer Res. , 46 , 4221 – 4224 ( 1986. ). [PubMed] [Google Scholar]
- 10. ) Watanabe , Y. , Endo , K. , Koizumi , M. , Sakahara , H. , Kawamura , Y. , Saga , T. , Konishi , J. , Ohshio , G. , Manabe , T. and Tobe , R.Semiquantitative in vitro binding assay of indium‐111‐labeled monoclonal antibodies to human cancer and normal tissues . J. Nucl. Med. , 29 , 1436 – 1442 ( 1988. ). [PubMed] [Google Scholar]
- 11. ) Halpern , S. E. , Dillman , R. O. , Witztum , K. F. , Shega , J. F. , Hagan , P. L. , Burrows , W. M. , Dillman , J. B. , Clutter , M. L. , Sobol , R. E. , Frincke , J. M. , Bartholomew , R. M. , David , G. S. and Carlo , D. J.Radioimmunodetection of melanoma utilizing 111In 96.5 monoclonal antibody: a preliminary report . Radiology , 155 , 493 – 499 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Krizan , Z. , Murray , J. L. , Hersh , E. M. , Rosenblum , M. G. , Glenn , H. J. , Gschwind , C. R. and Carlo , D. J.Increased labeling of human melanoma cells in vitro using combinations of monoclonal antibodies recognizing separate cell surface antigenic determinants . Cancer Res. , 45 , 4904 – 4909 ( 1985. ). [PubMed] [Google Scholar]
- 13. ) Herlyn , M. , Steplewski , Z. , Herlyn , D. and Koprowski , H.CO 17–1A and related monoclonal antibodies: their production and characterization . Hybridoma , 5 , Suppl. 1 , S3 – S10 ( 1986. ). [PubMed] [Google Scholar]
- 14. ) Sakahara , H. , Endo , K. , Nakajima , K. , Nakashima , T. , Koizumi , M. , Ohta , H. , Hidaka , A. , Kohno , S. , Nakano , Y. , Naito , A. , Suzuki , T. and Torizuka , K.Serum CA 19–9 concentrations and computed tomography findings in patients with pancreatic carcinoma . Cancer , 57 , 1324 – 1326 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Kuroki , M. , Arakawa , F. , Higuchi , H. , Matsunaga , A. , Okamoto , N. , Takakura , K. and Matsuoka , Y.Epitope mapping of the carcinoembryonic antigen by monoclonal antibodies and establishment of a new improved radio‐immunoassay system . Jpn. J. Cancer Res. , 78 , 386 – 396 ( 1987. ). [PubMed] [Google Scholar]
- 16. ) Koprowski , H. , Herlyn , M. , Steplewski , Z. and Sears , H. F.Specific antigen in serum of patients with colon carcinoma . Science , 212 , 53 – 55 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Magnani , J. L. , Brockhaus , M. , Smith , D. F. , Ginsburg , V. , Blaszczyk , M. , Mitchell , K. F. , Steplewski , Z. and Koprowski , H.A monosialoganglioside is a monoclonal antibody‐defined antigen of colon carcinoma . Science , 212 , 55 – 56 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Matsuoka , Y. , Kuroki , M. , Koga , Y. , Kuriyama , H. , Mori , T. and Kosaki , G.Immunochemical differences among carcinoembryonic antigen in tumor tissues and related antigens in meconium and adult feces . Cancer Res. , 42 , 2012 – 2018 ( 1982. ). [PubMed] [Google Scholar]
- 19. ) Magnani , J. L. , Steplewski , Z. , Koprowski , H. and Ginsburg , V.Identification of the gastrointestinal and pancreatic cancer‐associated antigen detected by monoclonal antibody 19–9 in the sera of patients as a mucin . Cancer Res. , 43 , 5489 – 5492 ( 1983. ). [PubMed] [Google Scholar]
- 20. ) Sakahara , H. , Endo , K. , Nakashima , T. , Ohta , H. , Torizuka , K. , Okada , K. , Yoshida , O. and Hirai , H.Basic studies on the tumor imaging using antibodies to human α‐fetoprotein . Jpn. J. Nucl. Med. , 21 , 805 – 813 ( 1984. ). [PubMed] [Google Scholar]
- 21. ) Lindmo , T. , Boven , E. , Cuttitta , F. , Fedorko , J. and Bunn , P. A. J.Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess . J. Immunol. Methods , 72 , 77 – 89 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Klug , T. L. , Salzman , S. , Quinn , A. , Melincoff , G. A. , Sedmak , D. D. , Tubbs , R. R. and Zurawski , V. R. , Jr.Tumorigenicity in athymic mice of the human colon carcinoma cell line SW1116 expressing the tumor‐associated antigenic determinant CA 19–9 . Cancer Res. , 44 , 5212 – 5218 ( 1987. ). [PubMed] [Google Scholar]
- 23. ) Watanabe , Y. , Endo , K. , Koizumi , M. , Kawamura , Y. , Saga , T. , Sakahara , H. , Kuroki , M. , Matsuoka , Y. and Konishi , J.Effect of tumor mass and antigenic nature on the biodistribution of labeled monoclonal antibodies . Cancer Res. , 49 , 2884 – 2889 ( 1989. ). [PubMed] [Google Scholar]
- 24. ) Pimm , M. V. and Baldwin , R. W.Localization of an anti‐tumor monoclonal antibody in human tumor xenografts: kinetic and quantitative studies with the 791T/36 antibody . In “ Monoclonal Antibodies for Cancer Detection and Therapy ,” ed. Baldwin R. W. and Byers V. S. , pp. 97 – 128 ( 1985. ). Academic Press, Inc. , London . [Google Scholar]
- 25. ) Munz , D. L. , Alavi , A. , Koprowski , H. and Herlyn , D.Improved radioimmunoimaging of human tumor xenografts by a mixture of monoclonal antibody F(ab′)2 fragments . J. Nucl Med. , 27 , 1739 – 1745 ( 1986. ). [PubMed] [Google Scholar]
- 26. ) Siccardi , A. G. , Buraggi , G. L. , Callegaro , L. , Centi Collela , A. , De Filippi , P. G. , Galli , G. , Mariani , G. , Masi , R. , Palumbo , R. , Riva , P. , Salvatore , M. , Scassellati , G. A. , Scheidhauer , K. , Turco , G. L. , Zaniol , P. , Benini , S. , Deleide , G. , Gasparini , M. , Lastoria , S. , Mansi , L. , Paganelli , G. , Salvischiani , E. , Seregni , E. , Viale , G. and Natali , P. G.Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab′)2 fragments of an anti‐carcinoembryonic antigen monoclonal antibody: a multi‐center study . Cancer Res. , 49 , 3096 – 3103 ( 1989. ). [PubMed] [Google Scholar]
- 27. ) Sharkey , R. M. , Primus , F. J. , Shochat , D. and Goldenberg , D. M.Comparison of tumor targeting of mouse monoclonal and goat polyclonal antibodies to carcinoembryonic antigen in the GW‐39 human tumor‐hamster host model . Cancer Res. , 48 , 1823 – 1828 ( 1988. ). [PubMed] [Google Scholar]
- 28. ) Wahl , R. L. , Parker , C. W , and Philpott , G. W.Improved radioimaging and tumor localization with monoclonal F(ab′)2 . J. Nucl. Med. , 24 , 316 – 325 ( 1983. ). [PubMed] [Google Scholar]
- 29. ) Matzku , S. , Kirchgessner , H. , Schmid , U. , Temponi , M. and Ferrone , S.Melanoma targeting with a cocktail of monoclonal antibodies to distinct determinants of the human HMW‐MAA . J. Nucl. Med. , 30 , 390 – 397 ( 1989. ). [PubMed] [Google Scholar]